We present a human-in-the-loop evaluation framework for fact-checking novel misinformation claims and identifying social media messages that violate relevant policies. Our approach extracts structured representations of check-worthy claims, which are aggregated and ranked for review. Stance classifiers are then used to identify tweets supporting novel misinformation claims, which are further reviewed to determine whether they violate relevant policies. To demonstrate the feasibility of our approach, we develop a baseline system based on modern NLP methods for human-in-the-loop fact-checking in the domain of COVID-19 treatments. Using our baseline system, we show that human fact-checkers can identify 124 tweets per hour that violate Twitter's policies on COVID-19 misinformation. We will make our code, data, and detailed annotation guidelines available to support the evaluation of human-in-the-loop systems that identify novel misinformation directly from raw user-generated content.